Optimisation of two-photon induced cleavage of molecular linker systems for drug delivery

Photoreactive linker systems for drug delivery in modern ophthalmology are crucial for the efficiency of such applications. We compare 5 different linker molecule candidates (truxillic acid and 4 dimers of coumarin derivates) in solution regarding their chemical stability and two-photon induced cleavage efficiency, and shed light into the role of molecular structure in the cleavage reaction. Dimers of the coumarin family showed much higher two-photon induced cleavage efficiency, achieving the highest reaction cross-section when tert-Butyldimethylsilyl (TBS) was used as a substituent, being almost 5-times higher than the unsubstituted coumarin dimer. Coumarin-based linker systems react promptly with nucleophilic solvents, in particular with short chain alcohols. The polarity of such solvents which do not cause a lactone ring opening seems not to influence the cleavage of the cyclobutane ring in coumarin dimers.